1. Field of the Invention
The present invention relates to pharmaceutical compositions comprising antineoplaston agents.
2. Description of Related Art
The antineoplaston agents are a family of naturally occurring non-toxic compounds believed to play a role in health and disease by producing and maintaining cellular differentiation. Antineoplaston agents are currently synthesized chemically but were initially isolated and characterized as natural constituents of body fluids. Among others, members of the antineoplaston family include 3-phenylacetyl-amino-2,6, piperidinedione (CN) and hydrolysis derivatives of CN: phenylacetylglutamine (PG) and iso-phenylacetylglutamine (Iso-PG), and phenylacetate (PN).
The three major forms of antineoplaston therapy, designated AS2-1, A-10, and CN therapies, are currently being evaluated for antineoplastic efficacy in multicenter phase II clinical trials. AS2-1 contains an 8:1 molar ratio of PN and L-PG and can be administered either intravenously or orally. A-10 therapy contains 4:1 molar ratio of PG and Iso-PG and is administered intravenously. Each of the A-10 components is racemic and optically inactive. CN therapy is a monotherapy consisting of racemic (optically inactive) CN that is administered orally.
In vitro dose-response studies on the individual components of antineoplaston therapy demonstrate that, on a molar basis, CN has the most potent antineoplastic activity. A problematic feature of CN, however, is that its solubility limits the highest testable concentration to .about.0.8 mM. At this concentration, CN produces only a 50% suppression of cell growth. The other, less potent, antineoplaston agents have higher solubility and this allows their intrinsically lower potency to be off-set by higher (e.g., 30 mM) concentrations. As a result of these higher concentrations, the less active antineoplaston agents (on a molar basis) produce a more complete suppression of cell growth. The uniquely non-toxic characteristics of the soluble antineoplastons allow plasma levels to be increased to a level well above that needed to suppress in vitro cell growth. However, with the less soluble antineoplastons such as CN, this strategy cannot be employed and alternative methods must be developed to increase CN solubility and cellular uptake.